We have found that thermal analogs of proteins, or thermal proteins, can be synthesized by simply heating .alpha.-amino acids (U.S. Pat. Nos. 3,052,655 and 3,076,790). Such thermal polymers have found utility in the microencapsulation of an antitumor agent (U.S. Pat. No. 4,963,364), as an artificial skin (U.S. Pat. No. 4,996,292) in the production of photographic film (U.S. Pat. No. 4,315,072), and in a photovoltaic device (U.S. Pat. No. 4,514,584).
In addition, Sikes and Wheeler found thermal proteins to possess utility as inorganic ion chelators (U.S. Pat. No. 4,534,881). Also, Steiner and Rosen found thermal proteins to have utility for the microencapsulation of numerous types of pharmaceuticals (U.S. Pat. Nos. 4,925,673 and 4,976,968).
Recently, some thermal proteins were found to have neurotrophic properties on cultured fetal rat forebrain neurons (Hefti et al, 1991). Such thermal proteins stimulated neural outgrowth and increased contact with other neurons, as well as prolonging the survival of neural cells. Altered synaptic connections within neural networks has been a basic underlying assumption of the mechanism by which the long term storage of information in the central nervous system occurs (Hebb, 1949). As some thermal proteins were found to promote the formation of synaptic connections within neural networks, it was hypothesized that such thermal proteins might enhance memory processing.
A number of chemical compounds exist which have been shown to improve memory when administered to mice and/or human subjects. Such compounds include nicotine, caffeine, amphetamine, strychnine, picrotoxin, corticosterone, ACTH, hydergine (Flood et al, 1985), and fluoxetine (Flood and Cherkin, 1987).
Memory enhancing compounds can be defined as compounds that: show a relationship between dose and degree of memory improvement; have a time-dependent action such that the longer the compound is administered after training the less effectively it improves memory; act as anti-amnestics; improve memory in more than one task; improve retention when administered before training, at a lower dose than when administered after training; improve retention when administered just prior to a retention test; and improve retention when administered centrally.
As numerous proteins and peptides are known to have various neurological effects, the object of this invention is the synthesis and identification of thermal proteins which have the neurological effect of improving memory processing.